The long-term objective of the proposed study is to uncover the factors which in experimental or clinical circumstances regulate the intensity of host responses to tumor related antigens and the kinds of immune substances that are formed in response to such antigens. This information will be obtained largely through the study of allografts of normal and neoplastic tissues in congenic-resistant strains of mice that differ with respect to weak transplantation antigens. We plan to study the influence of the form in which weak transplantation antigens are presented to the immune apparatus, the action of non-specific activators of immune function, reversal of states of specific non- responsiveness and the role of protective antibodies or blocking factors. It is intended that the data obtained in such studies will be important in devising approaches to immunotherapy of cancer in man.